CiteULike: Author Pizzo

Mast cell activators: a new class of highly effective vaccine adjuvants

James Mclachlan — 2008-05-08T08:03:42-00:00

Nature Medicine, Vol. 14, No. 5. (20 April 2008), pp. 536-541.

Mast cells (MCs) have recently received recognition as prominent effectors in the regulation of immune cell migration to draining lymph nodes and lymphocyte activation. However, their role in the development of humoral immune responses is not clear. Here, we demonstrate that subcutaneous or nasal administration of small-molecule MC activators with vaccine antigens evokes large increases in antigen-specific serum immunoglobulin G (IgG) responses. These responses were MC dependent and correlated with increased dendritic cell and lymphocyte recruitment to draining lymph nodes. Nasal instillation of these formulations also evoked antigen-specific secretory IgA and provided protection against anthrax lethal toxin challenge in vitro and against vaccinia virus infection in vivo. Collectively, these results define the MC as an integral sensory arm of the adaptive immune system. Moreover, they highlight MC activators as a new class of vaccine adjuvants, capable of inducing protective antigen-specific immune responses through needle-free routes of administration.

A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy.

A Freifeld — 2008-07-11T04:04:44-00:00

The New England journal of medicine, Vol. 341, No. 5. (29 July 1999), pp. 305-311.

BACKGROUND: Among patients with fever and neutropenia during chemotherapy for cancer who have a low risk of complications, oral administration of empirical broad-spectrum antibiotics may be an acceptable alternative to intravenous treatment. METHODS: We conducted a randomized, double-blind, placebo-controlled study of patients (age, 5 to 74 years) who had fever and neutropenia during chemotherapy for cancer. Neutropenia was expected to be present for no more than 10 days in these patients, and they had to have no other underlying conditions. Patients were assigned to receive either oral ciprofloxacin plus amoxicillin-clavulanate or intravenous ceftazidime. They were hospitalized until fever and neutropenia resolved. RESULTS: A total of 116 episodes were included in each group (84 patients in the oral-therapy group and 79 patients in the intravenous-therapy group). The mean neutrophil counts at admission were 81 per cubic millimeter and 84 per cubic millimeter, respectively; the mean duration of neutropenia was 3.4 and 3.8 days, respectively. Treatment was successful without the need for modifications in 71 percent of episodes in the oral-therapy group and 67 percent of episodes in the intravenous-therapy group (difference between groups, 3 percent; 95 percent confidence interval, -8 percent to 15 percent; P=0.48). Treatment was considered to have failed because of the need for modifications in the regimen in 13 percent and 32 percent of episodes, respectively (P<0.001) and because of the patient's inability to tolerate the regimen in 16 percent and 1 percent of episodes, respectively (P<0.001). There were no deaths. The incidence of intolerance of the oral antibiotics was 16 percent, as compared with 8 percent for placebo (P=0.07). CONCLUSIONS: In hospitalized low-risk patients who have fever and neutropenia during cancer chemotherapy, empirical therapy with oral ciprofloxacin and amoxicillin-clavulanate is safe and effective.

Management of fever in patients with cancer and treatment-induced neutropenia.

PA Pizzo — 2008-07-11T03:57:32-00:00

The New England journal of medicine, Vol. 328, No. 18. (6 May 1993), pp. 1323-1332.

Plasminogen Structural Domains Exhibit Different Functions When Associated with Cell Surface GRP78 or the Voltage-dependent Anion Channel

Mario Gonzalez-Gronow — 2008-05-27T03:48:40-00:00

J. Biol. Chem., Vol. 282, No. 45. (9 November 2007), pp. 32811-32820.

Both the voltage-dependent anion channel and the glucose-regulated protein 78 have been identified as plasminogen kringle 5 receptors on endothelial cells. In this study, we demonstrate that kringle 5 binds to a region localized in the N-terminal domain of the glucose-regulated protein 78, whereas microplasminogen does so through the C-terminal domain of the glucose-regulated protein 78. Both plasminogen fragments induce Ca2+ signaling cascades; however, kringle 5 acts through voltage-dependent anion channel and microplasminogen does so via the glucose-regulated protein 78. Because trafficking of voltage-dependent anion channel to the cell surface is associated with heat shock proteins, we investigated a possible association between voltage-dependent anion channel and glucose-regulated protein 78 on the surface of 1-LN human prostate tumor cells. We demonstrate that these proteins co-localize, and changes in the expression of the glucoseregulated protein 78 affect the expression of voltage-dependent anion channel. To differentiate the functions of these receptor proteins, either when acting singly or as a complex, we employed human hexokinase I as a specific ligand for voltage-dependent anion channel, in addition to kringle 5. We show that kringle 5 inhibits 1-LN cell proliferation and promotes caspase-7 activity by a mechanism that requires binding to cell surface voltage-dependent anion channel and is inhibited by human hexokinase I. 10.1074/jbc.M703342200

Prediction of mesothelioma and lung cancer in a cohort of asbestos exposed workers.

Antonio Gasparrini — 2008-05-09T08:32:35-00:00

European journal of epidemiology (26 April 2008)

Background Several papers have reported state-wide projections of mesothelioma deaths, but few have computed these predictions in selected exposed groups. Objective To predict the future deaths attributable to asbestos in a cohort of railway rolling stock workers. Methods The future mortality of the 1,146 living workers has been computed in term of individual probability of dying for three different risks: baseline mortality, lung cancer excess, mesothelioma mortality. Lung cancer mortality attributable to asbestos was calculated assuming the excess risk as stable or with a decrease after a period of time since first exposure. Mesothelioma mortality was based on cumulative exposure and time since first exposure, with the inclusion of a term for clearance of asbestos fibres from the lung. Results The most likely range of the number of deaths attributable to asbestos in the period 2005-2050 was 15-30 for excess of lung cancer, and 23-35 for mesothelioma. Conclusion This study provides predictions of asbestos-related mortality even in a selected cohort of exposed subjects, using previous knowledge about exposure-response relationship. The inclusion of individual information in the projection model helps reduce misclassification and improves the results. The method could be extended in other selected cohorts.

Root resorption and orthodontic treatment. Review of the literature.

G Pizzo — 2007-11-05T19:56:22-00:00

Minerva Stomatol, Vol. 56, No. 1-2. (b 2007), pp. 31-44.

The aim of this paper was to provide a systematic review of the literature on the root resorption caused by orthodontic treatment. Original papers on this subject, published in English from January 2000 until December 2005, were located in the MEDLINE/PubMed database. Other sources were taken from the references of the selected papers. Root resorption is the most common sequela of the orthodontic treatment. It is an inflammatory process that leads to an ischemic necrosis localized in the periodontal ligament when the orthodontic force is applied. The onset and progression of root resorption are associated with risk factors related to the orthodontic treatment such as the duration of treatment, the magnitude of the force applied, the direction of the tooth movement, the method of force application (continuous versus intermittent), the orthodontic movement. Patient-related risk factors are the individual susceptibility on a genetic basis, some systemic diseases, anomalies in root morphology, dental trauma, and previous endodontic treatment. The prevention of root resorption during the orthodontic treatment may be performed controlling the risk factors. The periodic radiographic control during the treatment is necessary in order to detect the occurrence of root damages and quickly reassess the treatment goals.

High failure rate of dapsone and pentamidine as Pneumocystis carinii pneumonia prophylaxis in human immunodeficiency virus-infected children.

SA Nachman — 2007-10-12T09:29:58-00:00

Pediatr Infect Dis J, Vol. 13, No. 11. (November 1994), pp. 1004-1006.

Three level rectifier versus three level inverter with DTC controlled induction motor

G Brando — 2007-01-25T16:13:38-00:00

Power Electronics and Drive Systems, 2003. PEDS 2003. The Fifth International Conference on, Vol. 2 (2003), pp. 1286-1290 Vol.2.

A three level NPC-rectifier versus three level NPC-inverter with direct torque controlled asynchronous motor is examined. Three level inverters have the problem of the DC-link voltage balance, especially if DTC control is considered. To reduce the problem both DC voltage and the potential of its middle point are controlled through a three level V.S.R. An appropriate feedback control is proposed to make the V.S.R. able to impose in the network nearly sinusoidal currents with unity power factor. The proposed control scheme is verified by means of simulations under significant conditions; the results are presented and discussed.

Choline Transporter 1 Maintains Cholinergic Function in Choline Acetyltransferase Haploinsufficiency

Eugene Brandon — 2006-10-10T06:10:00-00:00

J. Neurosci., Vol. 24, No. 24. (16 June 2004), pp. 5459-5466.

Choline acetyltransferase (ChAT), the enzyme that synthesizes the neurotransmitter acetylcholine (ACh), is thought to be present in kinetic excess in cholinergic neurons. The rate-limiting factor in ACh production is the provision of choline to ChAT. Cholinergic neurons are relatively unique in their expression of the choline transporter 1 (CHT1), which exhibits high-affinity for choline and catalyzes its uptake from the extracellular space to the neuron. Multiple lines of evidence indicate that the activity of CHT1 is a key determinant of choline supply for ACh synthesis. We examined the interaction of ChAT and ChT activity using mice heterozygous for a null mutation in the Chat gene (Chat+/-). In these mice, brain ChAT activity was reduced by 40-50% relative to the wild type, but brain ACh levels as well as ACh content and depolarization-evoked ACh release in hippocampal slices were normal. However, the amount of choline taken up by CHT1 and ACh synthesized de novo from choline transported by CHT1 in hippocampal slices, as well as levels of CHT1 mRNA in the septum and CHT1 protein in several regions of the CNS, were 50-100% higher in Chat+/- than in Chat+/+ mice. Thus, haploinsufficiency of ChAT leads to an increased expression of CHT1. Increased ChT activity may compensate for the reduced ChAT activity in Chat+/- mice, contributing to the maintenance of apparently normal cholinergic function as reflected by normal performance of these mice in several behavioral assays. 10.1523/JNEUROSCI.1106-04.2004

Chelation of cytoplasmic Ca2+ increases plasma membrane permeability in murine macrophages.

E Picello — 2006-02-12T22:31:06-00:00

J Biol Chem, Vol. 265, No. 10. (5 April 1990), pp. 5635-5639.

Cytoplasmic free Ca2+ (Ca2+i) was chelated to 10-20 nM in the macrophage cell line J774 either by incubation with quin2 acetoxymethyl ester in the absence of external Ca2+ (Di Virgilio, F., Lew, P.D., and Pozzan, T. (1984) Nature 310, 691-693) or by loading [ethyl-enebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) into the cytoplasm via reversible permeabilization of the plasma membrane with extracellular ATP (Steinberg, T.H., Newman, A.S., Swanson, J.A., and Silverstein, SS.C. (1987) J. Biol. Chem. 262, 8884-8888; Di Virgilio, F., Meyer, B.C., Greenberg, S., and Silverstein, S.C. (1988) J. Cell Biol. 106, 657-666). After removal of ATP from the incubation medium, ATP-permeabilized Ca2+i-depleted macrophages recovered a near-normal plasma membrane potential which slowly depolarized over a 2-4 h incubation at low [Ca2+]i. In both ATP-treated and quin2-loaded cells, depolarization of plasma membrane potential was paralleled by an increase in plasma membrane permeability to low molecular weight aqueous solutes such as eosin yellowish (Mr 692), ethidium bromide (Mr 394), and lucifer yellow (Mr 463). This increased plasma membrane permeability was not accompanied by release of the cytoplasmic marker lactic dehydrogenase for incubations up to 4 h and was likely a specific effect of Ca2+i depletion since it was not caused by: (i) the mere incubation of macrophages with extracellular EGTA, i.e. at near-normal [Ca2+]i; and (ii) loading into the cytoplasm of diethylenetriaminepentaacetic acid, a specific chelator of heavy metals with low affinity for Ca2+. Treatment of Ca2+i-depleted cells with direct (phorbol 12-myristate 13-acetate) or indirect (platelet-activating factor) activators of protein kinase C prevented the increase in plasma membrane permeability. Down-regulation of protein kinase C rendered Ca2+i-depleted macrophages refractory to the protective effect of phorbol 12-myristate 13-acetate. This report suggests a role for Ca2+i and possibly protein kinase C in the regulation of plasma membrane permeability to low molecular weight aqueous solutes.

Time-place learning in the eight-arm radial maze

Matthew Pizzo — 2004-12-28T16:32:41-00:00

Learning & Behavior, Vol. 32, No. 2., 240.

Cellular expression and alternative splicing of SLC25A23, a member of the mitochondrial Ca2+-dependent solute carrier gene family.

MT Bassi — 2005-08-27T13:05:11-00:00

Gene, Vol. 345, No. 2. (31 January 2005), pp. 173-182.

The transport of metabolites across the inner mitochondrial membrane is mediated by a large superfamily of mitochondrial solute carrier (MSC) proteins. A novel human member of the MSC gene family named SLC25A23, with homologs in mammalian and non-mammalian species has been recently identified together with two close paralogs, SLC25A24 and SLC25A25. These genes encode the human isoforms of the ATP-Mg/Pi carrier described in whole mitochondria. We report here the cellular expression and alternative splicing of SLC25A23. The gene encodes a 468 amino acids polypeptide, named SCaMC-3, with a bipartite structure typical of calcium-binding mitochondrial solute carrier (CaMSC) proteins. The amino-terminal portion harbors three canonical EF-hand calcium-binding domains while the carboxyl-terminal portion of SCaMC-3 has the characteristic features of the MSC superfamily. Northern blot analysis reveals the presence of the transcript in brain, heart, skeletal muscle, liver and small intestine. The SLC25A23 gene undergoes alternative splicing suggesting a modular nature of the encoded product. Three out of four putative protein isoforms lack a significant portion of the third mitochondrial carrier signature. The most common SCaMC-3 isoform shows a mitochondrial subcellular localization when transfected in HeLa cells and is able to bind calcium by Ca(2+)-dependent mobility shift assays. We believe that our study will contribute to a better knowledge of this family of mitochondrial carriers.